Summary
Previous studies have described a pharmacokinetic interaction between probenecid, a uricosuric drug, and oxipurinol, the major metabolite of allopurinol. In single dose studies, no interaction was found to occur between benzbromarone, another uricosuric agent, and oxipurinol.
A cross over study was conducted in 12 volunteers to compare the kinetics of allopurinol and oxipurinol following treatment for 7 days with allopurinol alone or combined with benzbromarone 20 or 100 mg.
The pharmacokinetic parameters of allopurinol were not modified by the uricosuric therapy, but those of oxipurinol were markedly altered by concurrent administration even of the lower dose of benzbromarone; the average plasma level fell by 30% and the renal elimination rate was increased by 50%.
A parallel increase in the renal elimination rate of uric acid was observed (significant only with the higher dose of benzbromarone) and a positive linear correlation between the fractional excretion of uric acid and that of oxipurinol was established.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Elion GB, Yü TF, Gutman AB, Hitchings GH (1968) Renal clearance of oxipurinol, the chief metabolite of allopurinol. Am J Med 45: 69–77
Von Löffler W, Gröbner W, Zöllner N (1983) Harnsäuresenkende Wirkung einer Kombination von Benzbromaron und Allopurinol — Untersuchungen unter standardisierten Ernährungsbedingungen. Arzneimittelforsch/Drug Res 33 [12]: 1687–1691
Von Arntz HR, Dreykluft HR, Leonhardt H (1979) Wirkung Harnsäure-senkender Medikamente in niedriger Dosierung. Fortschr Med 97 [27]: 1212–1214
Breithaupt H, Tittel M (1982) Kinetics of allopurinol after single intravenous and oral doses. Noninteraction with benzbromarone and hydrochlorothiazide. Eur J Clin Pharmacol 22: 77–84
David P, Chéron HM, Riopel-Crebessegues D (1984) Evaluations de la biodisponibilité et de la résultante hypouricémiante de l'anurate*: association allopurinol-benzbromarone. Acta Pharm Biol Clin 3: 337–339
Jain AK, Ryan JR, McMahon FG, Noveck RJ (1974) Effect of single oral doses of benzbromarone on serum and urinary uric acid. Arthritis Rheum 17 [2]: 149–157
Von Rüffer C, Zorn G, Henkel E, Mitzkat HJ (1982) Der Einfluß von Benzbromaron auf Pharmakokinetik und Pharmakodynamik von Oxipurinol. Arzneimittelforsch/Drug Res 32 [9]: 1149–1152
Failler JM, Farinotti R, Dauphin A (1985) Quantitative liquid chromatography of allopurinol and oxipurinol in human plasma and urine. Ther Drug Monit 33 [12]: 1687–1691
Yamaoka K, Nakagawa T, Uno T (1978) Statistical moments in pharmacokinetics. J Pharmacokinet Biopharm 6: 547–558
Mertz DP, Borner K (1983) Ausscheidung und Serumkonzentrationen von Allopurinol, Oxipurinol und Oxipurinen unter kombinierter Behandlung mit Allopurinol/Benzbromaron in steigender Dosierung. Med Welt 36: 974–979
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Colin, J.N., Farinotti, R., Fredj, G. et al. Kinetics of allopurinol and oxipurinol after chronic oral administration. Interaction with benzbromarone. Eur J Clin Pharmacol 31, 53–58 (1986). https://doi.org/10.1007/BF00870986
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00870986